Inhibition of c-jun n-terminal kinase attenuates diabetic testicular damage via endoplasmic reticulum stress reduction

The underlying causes of many diabetes-related complications are well known. However, the reasons for the complication related to male reproductive health remain unclear. Hyperglycemia disrupts the balance between oxidants and antioxidants, causing damage to cells, especially ER stress. ER stress triggered by the proteins accumulating in the ER lumen causes apoptosis by activating various pathways. c-Jun N-terminal kinase (JNK) is a key protein in systemic diseases like diabetes, and SP600125 is a widely used JNK inhibitor. This study focuses on whether JNK inhibition by SP600125 prevents diabetic testicular damage by reducing ER stress. In our study, animals were divided into three groups: Control group, the diabetes group, and the JNK inhibition group. Blood glucose level, body and testicular weights, and seminiferous tubule diameters were measured. Seminiferous tubules were evaluated by the Johnsen score in Hematoxyline and Eosin stained sections. Protein expressions of caspase 3, phospho (p)-JNK, caspase 12, and CHOP were evaluated. The Inhibitor group had significantly decreased active caspase-3, (p)-JNK, caspase-12, CHOP values, and blood glucose levels, increased body and testicular weights, seminiferous tubule diameter, and Johnsen score values compared to the diabetes group. JNK inhibition significantly ameliorated the histopathological damage in testicular tissue by preventing diabetes-induced ER stress and apoptosis.